This project focuses on physicochemical properties of nucleic acids as studied mainly by electron microscopy. A major objective is the elucidation of the intimate relationship between conformation of nucleic acid molecules and their biological function in living matter which is exerted by contact with other molecular components. By using simple model systems as well as gently isolated, mammalian chromatin, we are studying subtle and drastic changes in nucleic acid architecture. Of particular interest is the capacity of DNA to condense into compact particles with regular superstructure such as in chromatin, and the role of water, salts, and proteins in this process. Other major efforts aim at physical mapping of functional sites in extrachromosomal bacterial DNA's which carry resistance against antibiotics. This will be done by detection of AT-rich regions along DNA by partial strand separation within the double helix, and by means of restriction enzymes cleaving DNA at specific sites. Transcription of adenovirus DNA in cultured mammalian cells is analyzed by electron microcscopy of DNA:RNA hybrid molecules. BIBLIOGRAPHIC REFERENCES: Lang, D., Shaw, A.R. & McCorquodale, D.J. (1976). Molecular weights of DNA from bacteriophages T5, T5st(0), BF23, and BF23st(4). J. Virol. 176, 296-297. Taylor, T.N., Gray, D.M. & Lang, D. (1975) Response of linear and circular DNA to aqueous ethanol. TSEM Newsletter 6, No. 1.